The Developing CRC was funded in October 1992 in order to form a multi- disciplinary center of scientific excellence for studies and training in geriatric mood disorders. Mood disorders are highly prevalent and chronic in elderly populations and contribute to cognitive impairment, disability and mortality. The CRC's organizing principle has been that geriatric mood disorders are heterogenous syndromes best studied by clinical and biological investigations using outcomes as the principle validating parameter. This approach has yielded scientific evidence of subtypes of mood disorders with distinct clinical and biological characteristic and illness course. Beyond their heuristic value, these CRC findings have direct applicability to clinical practice. Fundamental to our success has been the CRC's achievement in recruitment (our goal was met) of a sample (N=235) with low attrition (total of 9.75 over 4 years), development of a well-managed database, and availability of advanced statistical support. Following the recommendations of the NIMH Study Section and its own external Advisory Committee the CRC has successfully created an atmosphere conductive to discovery and growth as evidenced by substantial increase in external funding (600%) in the past 4 years (12 R01 and R03 awards, 1 R24 grant for development of a Mental Health Services Research Program, 6 NIMH Career Development Awards and 4 Minority Supplements and Women's Studies grants). This application builds on these achievements and focuses on 3 over- arching themes: 1. long-term outcomes; 2. mechanisms, and 3. treatment of heterogenous geriatric mood disorders. The CRC has attracted new senior and junior investigators who enrich the scientific investigation and training. The Neuropsychology Core has added expertise in evoked potentials, structural and functional imaging. Medical and Psychosocial Cores are new to the CRC. We will expand the CRC sample by 400 subjects, including patients from medical (N=150), as well as psychiatric settings. These developments augment the CRC's histological strengths making possible integrative study of biology, medical co-morbidity, psychosocial characteristics, and both clinical and psychosocial outcomes in geriatric mood disorders.